scholarly journals Delayed-matching-to-position working memory in mice relies on NMDA-receptors in prefrontal pyramidal cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kasyoka Kilonzo ◽  
Bastiaan van der Veen ◽  
Jasper Teutsch ◽  
Stefanie Schulz ◽  
Sampath K. T. Kapanaiah ◽  
...  
Keyword(s):  
Working Memory ◽  
Pyramidal Cells ◽  
Cell Types ◽  
Delayed Matching ◽  
Hedonic Valuation ◽  
Distinct Cell ◽  
Excitatory Neurons ◽  
Processing Motivation ◽  
The Brain ◽  
Matching To Position

AbstractA hypofunction of N-methyl-D-aspartate glutamate receptors (NMDARs) has been implicated in the pathogenesis of schizophrenia by clinical and rodent studies. However, to what extent NMDAR-hypofunction in distinct cell-types across the brain causes different symptoms of this disease is largely unknown. One pharmaco-resistant core symptom of schizophrenia is impaired working memory (WM). NMDARs have been suggested to mediate sustained firing in excitatory neurons of the prefrontal cortex (PFC) that might underlie WM storage. However, if NMDAR-hypofunction in prefrontal excitatory neurons may indeed entail WM impairments is unknown. We here investigated this question in mice, in which NMDARs were genetically-ablated in PFC excitatory cells. This cell type-selective NMDAR-hypofunction caused a specific deficit in a delayed-matching-to-position (DMTP) 5-choice-based operant WM task. In contrast, T-maze rewarded alternation and several psychological functions including attention, spatial short-term habituation, novelty-processing, motivation, sociability, impulsivity, and hedonic valuation remained unimpaired at the level of GluN1-hypofunction caused by our manipulation. Our data suggest that a hypofunction of NMDARs in prefrontal excitatory neurons may indeed cause WM impairments, but are possibly not accounting for most other deficits in schizophrenia.

scholarly journals Triadimefon Disrupts Working Memory in the Matching-to-Position Task

SAGE Open ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 215824401880579
Author(s):  
John M. Holden ◽  
Ethan Hemmelman ◽  
Rowan McGlasson ◽  
Zaria Smith ◽  
Ashley Ruhland ◽  
...  
Keyword(s):  
Working Memory ◽  
Corn Oil ◽  
Acute Exposure ◽  
Male Rats ◽  
Sprague Dawley ◽  
Delayed Matching ◽  
Position Task ◽  
Matching To Position

Triadimefon (TDF) is a fungicide which has psychostimulant properties similar to cocaine and amphetamine. Past studies with psychostimulants suggests that acute exposure leads to disruptions in working memory. In this study, we examined the effects of TDF exposure (relative to corn oil control) on performance in the delayed matching-to-position task in two separate studies using Sprague-Dawley male rats. In both studies, TDF exposure led to significantly poorer performance across delays. TDF shows similar properties to cocaine and amphetamine in terms of disrupting working memory.

scholarly journals A single-cell transcriptomic atlas of the adult Drosophila ventral nerve cord

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Aaron M Allen ◽  
Megan C Neville ◽  
Sebastian Birtles ◽  
Vincent Croset ◽  
Christoph Daniel Treiber ◽  
...  
Keyword(s):  
Single Cell ◽  
Nerve Cord ◽  
Ventral Nerve Cord ◽  
Sensory Information ◽  
Neuronal Cell ◽  
Cell Types ◽  
Distinct Cell ◽  
Old Adult ◽  
And Behavior ◽  
The Brain

The Drosophila ventral nerve cord (VNC) receives and processes descending signals from the brain to produce a variety of coordinated locomotor outputs. It also integrates sensory information from the periphery and sends ascending signals to the brain. We used single-cell transcriptomics to generate an unbiased classification of cellular diversity in the VNC of five-day old adult flies. We produced an atlas of 26,000 high-quality cells, representing more than 100 transcriptionally distinct cell types. The predominant gene signatures defining neuronal cell types reflect shared developmental histories based on the neuroblast from which cells were derived, as well as their birth order. The relative position of cells along the anterior-posterior axis could also be assigned using adult Hox gene expression. This single-cell transcriptional atlas of the adult fly VNC will be a valuable resource for future studies of neurodevelopment and behavior.

scholarly journals Deciphering how specialized interneuron-specific cell types contribute to circuit function

2020 ◽  
Author(s):  
Alexandre Guet-McCreight ◽  
Frances K Skinner
Keyword(s):  
Computational Models ◽  
Brain Area ◽  
Pyramidal Cells ◽  
Cell Types ◽  
Specific Cell ◽  
Cell Type ◽  
Inhibitory Cell ◽  
Cell Firing ◽  
The Brain

AbstractThe wide diversity of inhibitory cells across the brain makes them fit to contribute to network dynamics in specialized fashions. However, the contributions of a particular inhibitory cell type in a behaving animal is challenging to decipher as one needs to both record cellular activities and identify the cell type being recorded. Thus, using computational modeling to explore cell-specific contributions so as to predict and hypothesize functional contributions is desirable. Here we examine potential contributions of interneuron-specific 3 (I-S3) cells - a type of inhibitory interneuron found in CA1 hippocampus that only targets other inhibitory interneurons - during simulated theta rhythms. We use previously developed multi-compartment models of oriens lacunosum-moleculare (OLM) cells, the main target of I-S3 cells, and explore how I-S3 cell inputs during in vitro and in vivo scenarios contribute to theta. We find that I-S3 cells suppress OLM cell spiking, rather than engender its spiking via post-inhibitory rebound mechanisms. To elicit recruitment similar to experiment, the inclusion of disinhibited pyramidal cell inputs is necessary, suggesting that I-S3 cell firing can broaden the window for disinhibiting pyramidal cells. Using in vivo virtual networks, we show that I-S3 cells can contribute to a sharpening of OLM cell recruitment at theta frequencies. Further, a shifting of the timing of I-S3 cell spiking due to external modulation can shift the timing of the OLM cell firing and thus disinhibitory windows. We thus propose a specialized contribution of I-S3 cells to create temporally precise coordination of modulation pathways.Significance StatementHow information is processed across different brain structures is an important question that relates to the different functions that the brain performs. In this work we use computational models that focus on a particular inhibitory cell type that only inhibits other inhibitory cell types – the I-S3 cell in the hippocampus. We show that this cell type is able to broaden the window for disinhibition of excitatory cells. We further illustrate that this broadening presents itself as a mechanism for input pathway switching and modulation over the timing of inhibitory cell spiking. Overall, this work contributes to our knowledge of how coordination between sensory and memory consolidation information is attained in a brain area that is involved in memory formation.

scholarly journals A multiple comparative study of putative endosymbionts in three coexisting apple snail species

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8125 ◽  
Author(s):  
Federico A. Dellagnola ◽  
Cristian Rodriguez ◽  
Alfredo Castro-Vazquez ◽  
Israel A. Vega
Keyword(s):  
Pyramidal Cells ◽  
Cell Types ◽  
Pomacea Canaliculata ◽  
Snail Species ◽  
Apple Snail ◽  
Multilamellar Bodies ◽  
Distinct Cell ◽  
Reported Data ◽  
Columnar Cells ◽  
Electron Lucent

We here compare morphological and molecular characters of some putative endosymbiotic elements of the digestive gland of three ampullariid species (Pomacea canaliculata, Pomacea scalaris and Asolene platae) which coexist in Lake Regatas (Palermo, Buenos Aires). The putative endosymbionts were reported in these species and were identified as C and K corpuscles. The three species show tubuloacinar glands, each adenomere was constituted mainly by two distinct cell types (columnar and pyramidal). C and K corpuscles together occupied from one-fourth to one-fifth of the tissue area in the three host species, where C corpuscles were round and greenish-brown, were delimited by a distinct wall, stained positively with Alcian Blue and were associated with columnar cells. K corpuscles were oval, dark-brown multilamellar bodies and were associated with pyramidal cells. Under TEM, C corpuscles occurred within vacuoles of columnar cells and contained many electron-dense clumps and irregular membrane stacks and vesicles spread in an electron-lucent matrix. Sometimes a membrane appeared detached from the inner surface of the wall, suggesting the existence of a plasma membrane. In turn, K corpuscles were contained within vacuoles of pyramidal cells and were made of concentric lamellae, which were in turn made of an electron-dense fibrogranular material. No membranes were seen in them. Interspecifically, C corpuscles vary significantly in width and inner contents. K corpuscles were also variable in length and width. However, both C and K corpuscles in the three studied species hybridised with generalised cyanobacterial/chloroplast probes for 16S rRNA. Also, both corpuscle types (isolated from gland homogenates) were sensitive to lysozyme digestion, which indicates that bacterial peptidoglycans are an integral part of their covers. The reported data confirm and extend previous studies on P. canaliculata in which the endosymbiotic nature of C and K corpuscles were first proposed. We further propose that the endosymbiotic corpuscles are related to the Cyanobacteria/chloroplasts clade. Based on the known distribution of these corpuscles in the major clades of Ampullariidae, we hypothesise they may be universally distributed in this family, and that may constitute an interesting model for studying the co-evolution of endosymbionts and their gastropod hosts.

Optogenetic and chemogenetic technologies for advanced functional investigations of the neural correlates of emotions

2019 ◽  
pp. 97-110
Author(s):  
Alexandre Surget ◽  
Catherine Belzung
Keyword(s):  
Human Subjects ◽  
Specific Area ◽  
Cell Types ◽  
Brain Lesions ◽  
Causal Relations ◽  
Neuronal Populations ◽  
Time Period ◽  
Distinct Cell ◽  
The Brain

The neural circuits underlying emotions have been extensively examined in the last decades, using either correlational approaches (e.g. functional imaging in human subjects or post-mortem immunohistochemistry in rodents) or methodologies enabling to investigate causal relationships (such as focused brain lesions in animals). However, each of these approaches has strong limitations that have hampered research in this field. The first approaches do not enable investigation of causal relations; they allow determining associations of particular emotional expressions with distinct cell populations or brain areas. The second approach enables the determination of causal relations but not the inhibition of particular cell types or projections or the investigation of the effects of manipulating neuronal activity during a restricted time period. Optogenetic and chemogenetic approaches are two cutting-edge methodologies that enabled ground-breaking research in the field of emotion in recent years. These approaches make possible the stimulation or inhibition of specific neuronal populations/projections in a specific area of the brain, during a precise period of time, thus permitting the dissection of the contribution of precise neuronal populations, sub-areas, and outputs to the different components of emotions. It is strongly impacting research in this field, providing a more complex and rich view of the biology of normal emotions.

scholarly journals Genetic identification Of brain cell types underlying schizophrenia

2017 ◽  
Author(s):  
Nathan G. Skene ◽  
Julien Bryois ◽  
Trygve E. Bakken ◽  
Gerome Breen ◽  
James J Crowley ◽  
...  
Keyword(s):  
Pyramidal Cells ◽  
Cell Types ◽  
Brain Cell ◽  
Common Variant ◽  
Genetic Identification ◽  
Medium Spiny Neurons ◽  
Gene Sets ◽  
The Common ◽  
The Brain ◽  
Brain Cell Types

AbstractWith few exceptions, the marked advances in knowledge about the genetic basis for schizophrenia have not converged on findings that can be confidently used for precise experimental modeling. Applying knowledge of the cellular taxonomy of the brain from single-cell RNA-sequencing, we evaluated whether the genomic loci implicated in schizophrenia map onto specific brain cell types. The common variant genomic results consistently mapped to pyramidal cells, medium spiny neurons, and certain interneurons but far less consistently to embryonic, progenitor, or glial cells. These enrichments were due to distinct sets of genes specifically expressed in each of these cell types. Many of the diverse gene sets associated with schizophrenia (including antipsychotic targets) implicate the same brain cell types. Our results provide a parsimonious explanation: the common-variant genetic results for schizophrenia point at a limited set of neurons, and the gene sets point to the same cells. While some of the genetic risk is associated with GABAergic interneurons, this risk largely does not overlap with that from projecting cells.

scholarly journals Overexpression of LIMK1 in hippocampal excitatory neurons improves synaptic plasticity and social recognition memory in APP/PS1 mice

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Haiwang Zhang ◽  
Youssif Ben Zablah ◽  
An Liu ◽  
Dongju Lee ◽  
Haorui Zhang ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Cell Types ◽  
Long Term Potentiation ◽  
Social Recognition ◽  
Cofilin Phosphorylation ◽  
Term Potentiation ◽  
Excitatory Neurons ◽  
Local Injections ◽  
The Brain

AbstractAccumulating evidence indicates that the actin regulator cofilin is overactivated in Alzheimer’s Disease (AD), but whether this abnormality contributes to synaptic and cognitive impairments in AD is unclear. In addition, the brain region and cell types involved remain unknown. In this study, we specifically manipulate LIMK1, the key protein kinase that phosphorylates and inactivates cofilin, in the hippocampus of APP/PS1 transgenic mice. Using local injections of the AAV virus containing LIMK1 under the control of the CaMKIIα promoter, we show that expression of LIMK1 in hippocampal excitatory neurons increases cofilin phosphorylation (i.e., decreases cofilin activity), rescues impairments in long-term potentiation, and improves social memory in APP/PS1 mice. Our results suggest that deficits in LIMK1/cofilin signaling in the hippocampal excitatory neurons contribute to AD pathology and that manipulations of LIMK1/cofilin activity provide a potential therapeutic strategy to treat AD.

Passive Dendritic Trees

1998 ◽  
Author(s):  
Christof Koch
Keyword(s):  
Nervous System ◽  
Morphological Structure ◽  
Pyramidal Cells ◽  
Quantitative Relationship ◽  
Cell Types ◽  
Dendritic Morphology ◽  
Granule Cell Layer ◽  
Dendritic Trees ◽  
A Cell ◽  
The Brain

The previous chapter dealt with the solution of the cable equation in response to current pulses and steps within a single unbranched cable. However, real nerve cells possess highly branched and extended dendritic trees with quite distinct morphologies. Figure 3.1 illustrates the fantastic variety of dendritic trees found throughout the animal kingdom, ranging from neurons in the locust to human brain cells and cells from many different parts of the nervous system. Some of these cells are spatially compact, such as retinal amacrine cells, which are barely one-fifth of a millimeter across, while some cells have immense dendritic trees, such as α motoneurones in the spinal cord extending across several millimeters. Yet, in all cases, neurons are very tightly packed: in vertebrates, peak density appears to be reached in the granule cell layer of the human cerebellum with around 5 million cells per cubic millimeter (Braitenberg and Atwood, 1958) while the packing density of the cells filling the 0.25 mm3 nervous system of the housefly Musca domestica is around 1.2 million cells per cubic millimeter (Strausfeld, 1976). The dendritic arbor of some cell types encompasses a spherical volume, such as for thalamic relay cells, while other cells, such as the cerebellar Purkinje cell, fill a thin slablike volume with a width less than one-tenth of their extent. Different cell types do not appear at random in the brain but are unique to specific parts of the brain. By far the majority of excitatory cells in the cortex are the pyramidal cells. Yet even within this class, considerable diversity exists. But why this diversity of shapes? To what extent do these quite distinct dendritic architectures reflect differences in their roles in information processing and computation? What influence does the dendritic morphology have on the electrical properties of the cell, or, in other words, what is the relationship between the morphological structure of a cell and its electrical function? One of the few cases where a quantitative relationship between form and some aspect of neuronal function has been established is the retinal neurons.

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